Molecular Medicine Reports
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2017
·Vol. 16
·期 6
·9189-9196
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IF 1.692
Xin Wang,Dalin Jia,Juncheng Zhang,Wei Wang
The aim of the present study was to observe the protective effect of grape seed proanthocyanidins (GSPs) against endoplasmic reticulum (ER) stress‑mediated apoptosis caused by hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes along with its potential mechanisms. H9C2 cardiomyocytes underwent hypoxia for 3 h followed by reoxygenation for 3 h. Different doses of GSPs (50, 100 and 200 µg/ml) were administered 30 min before hypoxia. Cell viability was assessed, as well as lactic dehydrogenase (LDH) activity, cell apoptosis rate, expression levels of glucose‑regulated protein 78 (GRP78), C/EBP‑homologous protein (CHOP), protein kinase RNA‑like ER kinase (PERK), and eukaryotic translation initiation factor‑2 (eIF2α) mRNA and protein. The results revealed that GSPs improved cell viability, reduced LDH activity and reduced the apoptosis rate in cells subjected to H/R, and that the protective effect was most significant when 100 µg/ml in GSPs was administered. GSPs treatment also decreased mRNA and protein expression of GRP78, CHOP, eIF2α and the level of the phosphorylated form of PERK. Furthermore, GSPs displayed a similar protective effect to that of established ER stress inhibitor 4‑phenyl butyric acid. In conclusion, the findings of this study suggest that GSPs may protect H9C2 cardiomyocytes from H/R injury by decreasing ER stress‑mediated apoptosis through the suppression of the PERK/eIF2α signaling pathway.
研究领域:
心脏病学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
FISH & SHELLFISH IMMUNOLOGY
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2025
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IF 3.9
Chuang Cui,Hao Liu,Yun-Fei Zhang,Ling-Ke Liu,Hai-Peng Liu
As obligate intracellular pathogens, viruses rely on the endoplasmic reticulum (ER) of host cells for viral protein synthesis and processing, leading to increased ER loading, which in turn triggers ER stress and activates the unfolded protein response (UPR). And this process is intricately linked to both viral infection and the host's immune response. White spot syndrome virus (WSSV) is one of the most detrimental viral pathogens affecting farmed crustaceans such as shrimp and crayfish, but the interaction between WSSV-induced ER stress and viral infection has not been comprehensively investigated. Here, we demonstrated that WSSV infection activated all three UPR pathways, including IRE1 pathway, ATF6 pathway and PERK-eIF2α pathway in crayfish hematopoietic tissue cells. In contrast to the promoted WSSV infection by IRE1 pathway and ATF6 pathway, the activated PERK-eIF2α pathway exhibited an inhibitory effect on viral infection, which was achieved via attenuation of global protein translation of host cells mediated by phosphorylation of eIF2α. Whereas, the continuous expression of WSSV proteins appeared to bypass this translational repression. Collectively, these results emphasized the key role of the PERK-eIF2α pathway, activated by WSSV-induced ER stress, in regulating viral infection, which might constitute an important aspect of the host cell's immune response to viral infection.
研究领域:
病毒学
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免疫学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
NanoImpact
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2020
·
IF 5.478
Tao Wang,Xiaozhen Wei,Yiru Sun,Yadong Hu,Jie Li,Xinyu Zhang,Shaowu Yin,Yonghai Shi,Yongxiang Zhu
Copper nanoparticles (CuNPs), a new pollutant in water environments, were widely used in various industrial and commercial applications. This study indicated that the presence of CuNPs exposure under environmental related concentration is an inducing factor that contributes to the fatty liver formation in Takifugu fasciatus . Furthermore, we explored the fatty liver formation mechanism. The results shown, (1) the cloned genes related to endoplasmic reticulum stress (ERS) ( GRP78, IRE-1α, PERK , and ATF-6α ) were highly expressed in the liver of T. fasciatus. (2) after 30-days exposure, CuNPs accumulated in the endoplasmic reticulum of liver and induced the appearance of ERS, then activated unfolded protein response (UPR) signaling pathway. Furthermore, the SREBP-1c pathway that plays a key role in lipid synthesis was activated. (3) by using 4-PBA and GSK inhibitors to respectively stimulate ERS and PKR-like ER kinase (PERK) through in vitro experiments, we confirmed that CuNPs induced the fatty liver formation in T. fasciatus triggered by the PERK-EIF2α pathway by activating the SREBP-1c pathway to promote fatty liver formation. This study provides a new perspective for identifying the pathogens of fatty liver formation, and adds to the knowledge of the ecological safety data service of CuNPs in water
研究领域:
环境科学
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分子生物学
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水生毒理学
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DOI
PubMed
高影响因子
Frontiers in Endocrinology
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2025
·
IF 4.6
Congrong Wu,Maomao Sun,Yue He,Jie Jiang,Luran Wang,Yanni Wang,Yonghui Yu
Background: Clinical research has identified a correlation between hypertensive disorders of pregnancy (HDP) and subclinical hypothyroidism during gestation. But the potential influence of HDP on thyroid hormone synthesis remains undetermined.Aims: This study aims to elucidate the impact of HDP on thyroid hormone synthesis and to delineate the underlying mechanisms.Methods: 20 pregnancy SD rats were stratified at random into the HDP group and the Control group. The HDP group was subjected to NG-Nitro-L-arginine-methylester administration from gestational days 13 to 20, while the Control group received saline. Subsequent assessments encompassed serum FT4, FT3, and TSH concentrations, morphological examination of the thyroid, as well as quantification of essential proteins pivotal to thyroid hormone synthesis and markers indicative of endoplasmic reticulum stress.Results: The HDP group exhibited a statistically significant augmentation in serum TSH concentrations (p<0.05), while FT3 and FT4 levels manifested no discernible statistical variations. H&E staining highlighted a pronounced hyperplasia of the follicular epithelial cells and a diminution in the follicle lumen area. Electron microscopy unveiled pronounced endoplasmic reticulum markedly swelling and expansion within the HDP group. Molecular evaluations revealed a decrement in Tg expression within thyroid tissue, concomitant with an upregulated expression of p-PERK, P-eIF2α, and ATF4.Conclusion: This investigation suggests that HDP might modulate Tg expression within thyroid tissue, possibly mediated through the PERK/eIF2α signaling cascade. This perturbation may compromise thyroid hormone synthesis, thereby predisposing pregnant rats to subclinical hypothyroidism.
研究领域:
内分泌学
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生殖医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
BRAIN RESEARCH BULLETIN
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2024
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IF 3.5
Yuqian Zhang,Shenghan Gao,Shengnan Xia,Haiyan Yang,Xinyu Bao,Qingxiu Zhang,Yun Xu
Due to various factors, there is still a lack of effective neuroprotective agents for ischemic stroke in clinical practice. Neuroinflammation and neuronal apoptosis mediated by endoplasmic reticulum stress are some of the important pathological mechanisms in ischemic stroke. Linarin has been reported to have anti-inflammation, antioxidant, and anti-apoptotic effects in myocardial ischemia, osteoarthritis, and kidney disease. Whether it exerts neuroprotective functions in ischemic stroke has not been investigated. The results showed that linarin could reduce the infarct volume in cerebral ischemia animal models, improve the neurological function scores and suppress the expression of inflammatory factors mediating the NF-κB. Meanwhile, it could protect the neurons from OGD/R-induced-apoptosis, which was related to the PERK-eIF2α pathway. Our results suggested linarin could inhibit neuronal inflammation and apoptosis induced by endoplasmic reticulum stress. Furthermore, the neuroprotective effect of linarin may be related to the inhibition of AKR1B1. Our study offers new insight into protecting against ischemia-reperfusion injury by linarin treatment in stroke.
研究领域:
神经科学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Acta Biomaterialia
·
2023
·
IF 9.7
Xiaoli Feng,Tian Lin,Dong Chen,Zhiyang Li,Qiuping Yang,Huiting Tian,Yao Xiao,Mingzhen Lin,Min Liang,Weihong Guo,Peng Zhao,Zhaoze Guo
Chemodynamic therapy (CDT) can effectively induce immunogenic cell death (ICD) in tumours and is thus a promising strategy for boosting the efficacy of immunotherapy. However, the mechanism by which CDT enhances ICD and lowers ICD efficiency is unknown and this restricts its clinical application. In this study, a second near-infrared (NIR-II) window irradiation-triggered hydrogen peroxide (H 2 O 2 ) self-supplying nanocomposite ((Cu 2 Se-CaO 2 )@LA) was constructed. The modified lauric acid was melted by the heat energy of the NIR-II irradiation, to expose the CaO 2 nanoparticles, and they then reacted with water to produce H 2 O 2 and Ca 2+ . H 2 O 2 was then converted to hydroxyl radicals by the photothermal-enhanced CDT process of the Cu 2 Se nanocubes. Notably, the CDT and Ca 2+ overload was found to induce sequential damage to the mitochondria and endoplasmic reticulum (ER), which upregulated the PERK-mediated eIF2α phosphorylation pathway and caused subsequent ICD. NIR-II irradiation of the (Cu 2 Se-CaO 2 )@LA also increased reactive oxygen species (ROS) formation and this was sufficient to increase dendritic cell maturation, attracting cytotoxic T lymphocytes, and suppressing tumour growth in vivo. Overall, we demonstrated that an enhanced CDT strategy under NIR-II exposure and H 2 O 2 self-supply can induce extensive ICD by inducing mitochondria-associated ER stress, which represents a highly effective and promising strategy for ICD amplification and tumour immunotherapy. Statement of significance In this study, a second near-infrared window (NIR-II) irradiation-triggered and H 2 O 2 self-supplying nanocomposite (named (Cu 2 Se-CaO 2 )@LA) was constructed and tested both in vitro and in vivo . These nanoparticles demonstrated promising antitumor activity as designed. Mechanistically, the nanoparticles could damage mitochondria and upregulate the PERK-mediated eIF2αphosphorylation pathway, further causing endoplasmic reticulum stress, and inducing immunogenic cell death through dendritic cell maturation and cytotoxic T lymphocyte recruitment augmented activity. This system represents a highly effective and promising strategy for enhancing tumor immunotherapy and provides new insights for future studies and design refinements.
研究领域:
癌症研究
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免疫治疗
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纳米技术
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细胞生物学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
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